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© The Rockefeller University Press, 0021-9525/1999//1235 $5.00
The Journal of Cell Biology, Volume 144, Number 6, , 1999 1235-1244

Rho GTPases Control Polarity, Protrusion, and Adhesion during Cell Movement

MRC Laboratory for Molecular Cell Biology, CRC Oncogene and Signal Transduction Group and Department of Biochemistry, University College London, London WC1E 6BT, United Kingdom

Cell movement is essential during embryogenesis to establish tissue patterns and to drive morphogenetic pathways and in the adult for tissue repair and to direct cells to sites of infection. Animal cells move by crawling and the driving force is derived primarily from the coordinated assembly and disassembly of actin filaments. The small GTPases, Rho, Rac, and Cdc42, regulate the organization of actin filaments and we have analyzed their contributions to the movement of primary embryo fibroblasts in an in vitro wound healing assay. Rac is essential for the protrusion of lamellipodia and for forward movement. Cdc42 is required to maintain cell polarity, which includes the localization of lamellipodial activity to the leading edge and the reorientation of the Golgi apparatus in the direction of movement. Rho is required to maintain cell adhesion during movement, but stress fibers and focal adhesions are not required. Finally, Ras regulates focal adhesion and stress fiber turnover and this is essential for cell movement. We conclude that the signal transduction pathways controlled by the four small GTPases, Rho, Rac, Cdc42, and Ras, cooperate to promote cell movement.

Key Words: Rho GTPases • Ras • polarity • focal adhesion • wound healing

Abbreviations used in this paper: GAP, GTPase-activating protein; REF, rat embryo fibroblast.

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• Guo, F., Debidda, M., Yang, L., Williams, D. A., Zheng, Y. (2006). Genetic Deletion of Rac1 GTPase Reveals Its Critical Role in Actin Stress Fiber Formation and Focal Adhesion Complex Assembly. J. Biol. Chem. 281: 18652-18659 [Abstract] [Full Text]  
• Lee, J. G., Kay, E. P. (2006). Cross-talk among Rho GTPases Acting Downstream of PI 3-Kinase Induces Mesenchymal Transformation of Corneal Endothelial Cells Mediated by FGF-2.. IOVS 47: 2358-2368 [Abstract] [Full Text]  
• Li, Z., Wang, C., Jiao, X., Lu, Y., Fu, M., Quong, A. A., Dye, C., Yang, J., Dai, M., Ju, X., Zhang, X., Li, A., Burbelo, P., Stanley, E. R., Pestell, R. G. (2006). Cyclin D1 Regulates Cellular Migration through the Inhibition of Thrombospondin 1 and ROCK Signaling.. Mol. Cell. Biol. 26: 4240-4256 [Abstract] [Full Text]  
• Lee, J. S. H., Panorchan, P., Hale, C. M., Khatau, S. B., Kole, T. P., Tseng, Y., Wirtz, D. (2006). Ballistic intracellular nanorheology reveals ROCK-hard cytoplasmic stiffening response to fluid flow.. J. Cell Sci. 119: 1760-1768 [Abstract] [Full Text]  
• Zhang, Z.-G., Bothe, I., Hirche, F., Zweers, M., Gullberg, D., Pfitzer, G., Krieg, T., Eckes, B., Aumailley, M. (2006). Interactions of primary fibroblasts and keratinocytes with extracellular matrix proteins: contribution of {alpha}2{beta}1 integrin.. J. Cell Sci. 119: 1886-1895 [Abstract] [Full Text]  
• Eisen, R., Walid, S., Ratcliffe, D. R., Ojakian, G. K. (2006). Regulation of epithelial tubule formation by Rho family GTPases. Am. J. Physiol. Cell Physiol. 290: C1297-C1309 [Abstract] [Full Text]  
• Kiener, H. P., Stipp, C. S., Allen, P. G., Higgins, J. M.G., Brenner, M. B. (2006). The Cadherin-11 Cytoplasmic Juxtamembrane Domain Promotes {alpha}-Catenin Turnover at Adherens Junctions and Intercellular Motility. Mol. Biol. Cell 17: 2366-2376 [Abstract] [Full Text]  
• Vidali, L., Chen, F., Cicchetti, G., Ohta, Y., Kwiatkowski, D. J. (2006). Rac1-null Mouse Embryonic Fibroblasts Are Motile and Respond to Platelet-derived Growth Factor. Mol. Biol. Cell 17: 2377-2390 [Abstract] [Full Text]  
• Sastry, S. K., Rajfur, Z., Liu, B. P., Cote, J.-F., Tremblay, M. L., Burridge, K. (2006). PTP-PEST Couples Membrane Protrusion and Tail Retraction via VAV2 and p190RhoGAP. J. Biol. Chem. 281: 11627-11636 [Abstract] [Full Text]  
• Lee, J. G., Kay, E. P. (2006). FGF-2-Induced Wound Healing in Corneal Endothelial Cells Requires Cdc42 Activation and Rho Inactivation through the Phosphatidylinositol 3-Kinase Pathway.. IOVS 47: 1376-1386 [Abstract] [Full Text]  
• Hirsch, D. S., Shen, Y., Wu, W. J. (2006). Growth and motility inhibition of breast cancer cells by epidermal growth factor receptor degradation is correlated with inactivation of cdc42.. Cancer Res. 66: 3523-3530 [Abstract] [Full Text]  
• Cernuda-Morollon, E., Ridley, A. J. (2006). Rho GTPases and Leukocyte Adhesion Receptor Expression and Function in Endothelial Cells. Circ. Res. 98: 757-767 [Abstract] [Full Text]  
• Kuo, J.-C., Wang, W.-J., Yao, C.-C., Wu, P.-R., Chen, R.-H. (2006). The tumor suppressor DAPK inhibits cell motility by blocking the integrin-mediated polarity pathway.. JCB 172: 619-631 [Abstract] [Full Text]  
• Reville, K., Crean, J. K., Vivers, S., Dransfield, I., Godson, C. (2006). Lipoxin A4 Redistributes Myosin IIA and Cdc42 in Macrophages: Implications for Phagocytosis of Apoptotic Leukocytes. J. Immunol. 176: 1878-1888 [Abstract] [Full Text]  
• Qin, C., Nagao, T., Grosheva, I., Maxfield, F. R., Pierini, L. M. (2006). Elevated Plasma Membrane Cholesterol Content Alters Macrophage Signaling and Function. Arterioscler. Thromb. Vasc. Bio. 26: 372-378 [Abstract] [Full Text]  

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